Different Effects of Antiepileptic Drugs on Initiation and Propagation of Ictal Discharges in a Case of Frontal Lobe Epilepsy

Abstract

Case Report: The subject was a 25‐year‐old woman with frequent complex partial seizures during sleep. She had a history of nocturnal seizures consisting of brief tonic extensions of the upper limbs and vocalizations since she was 15 years old. At age 20 years, she also developed other nocturnal seizures associated with urinary incontinence. She was hospitalized at our facility for seizure control. Neurologic examination and brain magnetic resonance imaging (MRI) were normal. Frequent seizures were captured with audiovisual/EEG monitoring during sleep. The seizures began with tonic extension of the upper limbs and moaning, occasionally followed by accelerated breathing. The duration of the seizures was brief (<30 s), and the patient was conscious at the beginning of the seizure. The ictal discharges showed diffuse fast waves with frontal predominance followed by diffuse slow waves. The ictal manifestations and ictal EEG findings seemed to indicate that these seizures originated in the frontal lobe. About 60 seizures were recorded during a night, half of which were not associated with any clinical symptoms. We referred to the discharges without any clinical symptoms as subclinical discharges to distinguish them from ictal discharges with clinical symptoms. Most of these ictal and subclinical discharges appeared during sleep stages 1 or 2, and were accompanied by stage shifts, including awakening. A sleep hypnogram showed very frequent awakenings and stage shifts. Before admittance, the patient was treated with valproate (VPA), phenobarbital (PB), primidone (PRM), and clonazepam (CZP). Then PB, PRM, and CZP were discontinued because VPA alone was considered to be effective. With VPA therapy, a polygraphic recording showed only a few seizures and several subclinical discharges. A hypnogram also showed a reduction in awakenings and stage shifts. However, urinary incontinence and secondarily generalized seizures were still observed. When carbamazepine (CBZ) was added to the VPA, the urinary incontinence and secondarily generalized seizures disappeared. Polygraphic recording revealed a few ictal and subclinical discharges. The frequency of awakening and stage shifts was decreased, and slow‐wave sleep (Stages 3 and 4) was increased. Thus the sleep structure became more stable. Then VPA was discontinued. With CBZ monotherapy, no clinical seizures were observed, hut ‐150 subclinical discharges were recorded polygraphically during a night, and extremely frequent stage shifts between sleep Stages 1 and 2 were observed. The sleep structure became more unstable. Conclusions: In this case, VPA therapy caused a decrease in the frequency of ictal and subclinical discharges, but did not suppress urinary incontinence and generalized seizures. CBZ, on the other hand, inhibited urinary incontinence and generalized seizures, but caused an increase in the number of subclinical discharges. This suggests that VPA suppressed the initiation of ictal discharges but not their propagation, whereas CBZ inhibited the propagation but not the initiation of ictal discharges. We, therefore, consider the antiepileptic effects of VPA and CBZ to be based on different mechanisms of action.